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Annual Review of Pathology-Mechanisms of Disease最新文献

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Exploring the Complex Pathophysiology of Necrotizing Enterocolitis in Preterm Neonates. 探讨早产儿坏死性小肠结肠炎的复杂病理生理学。
IF 36.2 1区 医学
Annual Review of Pathology-Mechanisms of Disease Pub Date : 2025-09-15 DOI: 10.1146/annurev-pathmechdis-070224-014223
Bo Li,Mina Yeganeh,Dorothy Lee,Sinobol Chusilp,Felicia Balsamo,Niloofar Ganji,Chen-Yi Wang,Andrea Zito,George Biouss,Agostino Pierro
{"title":"Exploring the Complex Pathophysiology of Necrotizing Enterocolitis in Preterm Neonates.","authors":"Bo Li,Mina Yeganeh,Dorothy Lee,Sinobol Chusilp,Felicia Balsamo,Niloofar Ganji,Chen-Yi Wang,Andrea Zito,George Biouss,Agostino Pierro","doi":"10.1146/annurev-pathmechdis-070224-014223","DOIUrl":"https://doi.org/10.1146/annurev-pathmechdis-070224-014223","url":null,"abstract":"Necrotizing enterocolitis (NEC) is the most common gastrointestinal emergency in preterm neonates, with a mortality rate of 30-50% in advanced cases. Despite decades of research, its multifactorial pathophysiology remains incompletely understood. This review summarizes recent advances in NEC research and proposes an integrative theoretical framework for its pathogenesis. We examine key contributing factors, including intestinal vascular development, mucosal immunity, intestinal regeneration, the enteric nervous system, and the gut microbiome, highlighting how prematurity disrupts these processes and predisposes neonates to NEC. Furthermore, we propose a sequential model of NEC pathogenesis, hypothesizing that impaired intestinal microcirculation in preterm neonates compromises blood flow in response to enteral feeding, leading to localized ischemia. This initiates epithelial barrier dysfunction, exacerbates inflammatory responses, impairs intestinal regeneration, and disrupts enteric nervous system function, collectively driving NEC progression. By integrating experimental and clinical findings, we provide a comprehensive perspective on NEC initiation in preterm neonates and identify potential avenues for future research and therapeutic interventions.","PeriodicalId":50753,"journal":{"name":"Annual Review of Pathology-Mechanisms of Disease","volume":"13 1","pages":""},"PeriodicalIF":36.2,"publicationDate":"2025-09-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145068438","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
Clonal Hematopoiesis in Nonmalignant Disease: Functional Consequences of Mutated Immune Cells by Clonal Hematopoiesis in the Diseased Tissue. 非恶性疾病中的克隆造血：病变组织中克隆造血导致免疫细胞突变的功能后果。
IF 36.2 1区 医学
Annual Review of Pathology-Mechanisms of Disease Pub Date : 2025-09-10 DOI: 10.1146/annurev-pathmechdis-111523-023442
Youngil Koh,Isak W Tengesdal,Siddhartha Jaiswal
{"title":"Clonal Hematopoiesis in Nonmalignant Disease: Functional Consequences of Mutated Immune Cells by Clonal Hematopoiesis in the Diseased Tissue.","authors":"Youngil Koh,Isak W Tengesdal,Siddhartha Jaiswal","doi":"10.1146/annurev-pathmechdis-111523-023442","DOIUrl":"https://doi.org/10.1146/annurev-pathmechdis-111523-023442","url":null,"abstract":"Clonal hematopoiesis, originally identified as a precursor to hematologic malignancies, has emerged as a significant factor in various nonmalignant diseases. Recent research highlights how somatic mutations in hematopoietic stem cells lead to the expansion of circulating mutated immune cells that exert profound effects on organ function and disease progression. These mutated clones display altered inflammatory profiles and tissue-specific functional consequences, contributing to various diseases including atherosclerotic cardiovascular disease, osteoporosis, heart failure, and neurodegenerative conditions. Key mutations, particularly in genes regulating epigenetics (TET2, DNMT3A, ASXL1), splicing (SF3B1, U2AF1), and DNA damage repair (TP53, PPM1D), modify immune responses and promote chronic inflammation. Intriguingly, while clonal hematopoiesis exacerbates many inflammatory conditions, it has been linked to a protective effect in Alzheimer's disease, potentially due to enhanced microglial function. Understanding the mechanistic underpinnings of clonal hematopoiesis in nonmalignant disease may inform targeted therapeutic strategies, particularly those aimed at modulating inflammation. This review explores the gene- and organ-specific roles of clonal hematopoiesis, highlighting its implications for disease pathogenesis and potential interventions.","PeriodicalId":50753,"journal":{"name":"Annual Review of Pathology-Mechanisms of Disease","volume":"45 1","pages":""},"PeriodicalIF":36.2,"publicationDate":"2025-09-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145031789","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
Fibroblast Modulation of Stem Cell Lineage Infidelity and Metaplasia in Tissue Fibrosis 成纤维细胞对组织纤维化中干细胞谱系不忠和化生的调节
IF 36.2 1区 医学
Annual Review of Pathology-Mechanisms of Disease Pub Date : 2025-08-21 DOI: 10.1146/annurev-pathmechdis-042624-111827
Tsukasa Kadota, Tien Peng
{"title":"Fibroblast Modulation of Stem Cell Lineage Infidelity and Metaplasia in Tissue Fibrosis","authors":"Tsukasa Kadota, Tien Peng","doi":"10.1146/annurev-pathmechdis-042624-111827","DOIUrl":"https://doi.org/10.1146/annurev-pathmechdis-042624-111827","url":null,"abstract":"Epithelial stem cells are segregated on the basis of region-specific identities during homeostasis. However, tissue perturbations can induce remarkable plasticity in stem cells to adopt lineage identities outside their anatomical compartments. This phenomenon has been termed lineage infidelity or metaplasia depending on the tissue, and the stem cell trajectory can determine regenerative outcomes relevant to many diseases, including fibrosis. While many studies have shed light on stem-cell intrinsic mechanisms that govern their ability to switch identities, much less is known about microenvironmental factors that alert stem cells and modify their lineage decisions. Fibroblasts are structural cells that provide the necessary scaffolding for stem cells in their native niche, but fibroblasts also sense external changes to the tissue environment to drive the tissue response. In this review, we explore the role of fibroblasts as a critical orchestrator of lineage plasticity that blurs compartmental identities to initiate proper repair or disease.","PeriodicalId":50753,"journal":{"name":"Annual Review of Pathology-Mechanisms of Disease","volume":"19 1","pages":""},"PeriodicalIF":36.2,"publicationDate":"2025-08-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144898420","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
Unraveling Mechanisms of Genetic Risks in Metabolic Dysfunction-Associated Steatotic Liver Diseases: A Pathway to Precision Medicine. 代谢功能障碍相关脂肪变性肝病遗传风险机制的揭示：通往精准医学的途径。
IF 28.4 1区 医学
Annual Review of Pathology-Mechanisms of Disease Pub Date : 2025-01-01 DOI: 10.1146/annurev-pathmechdis-111523-023430
Xiang Zhang, Kyong-Mi Chang, Jun Yu, Rohit Loomba
{"title":"Unraveling Mechanisms of Genetic Risks in Metabolic Dysfunction-Associated Steatotic Liver Diseases: A Pathway to Precision Medicine.","authors":"Xiang Zhang, Kyong-Mi Chang, Jun Yu, Rohit Loomba","doi":"10.1146/annurev-pathmechdis-111523-023430","DOIUrl":"10.1146/annurev-pathmechdis-111523-023430","url":null,"abstract":"<p><p>Metabolic dysfunction-associated steatotic liver disease (MASLD) is a growing global health problem, affecting ∼1 billion people. This condition is well established to have a heritable component with strong familial clustering. With the extraordinary breakthroughs in genetic research techniques coupled with their application to large-scale biobanks, the field of genetics in MASLD has expanded rapidly. In this review, we summarize evidence regarding genetic predisposition to MASLD drawn from family and twin studies. Significantly, we delve into detailed genetic variations associated with diverse pathogenic mechanisms driving MASLD. We highlight the interplay between these genetic variants and their connections with metabolic factors, the gut microbiome, and metabolites, which collectively influence MASLD progression. These discoveries are paving the way for precise medicine, including noninvasive diagnostics and therapies. The promising landscape of novel genetically informed drug targets such as RNA interference is explored. Many of these therapies are currently under clinical validation, raising hopes for more effective MASLD treatment.</p>","PeriodicalId":50753,"journal":{"name":"Annual Review of Pathology-Mechanisms of Disease","volume":"20 1","pages":"375-403"},"PeriodicalIF":28.4,"publicationDate":"2025-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143034746","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
Roles of Cellular Neighborhoods in Hepatocellular Carcinoma Pathogenesis. 细胞邻域在肝癌发病机制中的作用。
IF 28.4 1区 医学
Annual Review of Pathology-Mechanisms of Disease Pub Date : 2025-01-01 DOI: 10.1146/annurev-pathmechdis-111523-023520
Lichun Ma, Cherry Caiyi Li, Xin Wei Wang
{"title":"Roles of Cellular Neighborhoods in Hepatocellular Carcinoma Pathogenesis.","authors":"Lichun Ma, Cherry Caiyi Li, Xin Wei Wang","doi":"10.1146/annurev-pathmechdis-111523-023520","DOIUrl":"10.1146/annurev-pathmechdis-111523-023520","url":null,"abstract":"<p><p>The development of hepatocellular carcinoma (HCC) involves an intricate interplay among various cell types within the liver. Unraveling the orchestration of these cells, particularly in the context of various etiologies, may hold the key to deciphering the underlying mechanisms of this complex disease. The advancement of single-cell and spatial technologies has revolutionized our ability to determine cellular neighborhoods and understand their crucial roles in disease pathogenesis. In this review, we highlight the current research landscape on cellular neighborhoods in chronic liver disease and HCC, as well as the emerging computational approaches applicable to delineate disease-associated cellular neighborhoods, which may offer insights into the molecular mechanisms underlying HCC pathogenesis and pave the way for effective disease interventions.</p>","PeriodicalId":50753,"journal":{"name":"Annual Review of Pathology-Mechanisms of Disease","volume":"20 1","pages":"169-192"},"PeriodicalIF":28.4,"publicationDate":"2025-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143034739","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
Reflections on a Career in Pediatric Neuropathology, with a Note of Gratitude. 对儿科神经病理学职业生涯的思考，以及感恩之情。
IF 28.4 1区 医学
Annual Review of Pathology-Mechanisms of Disease Pub Date : 2025-01-01 Epub Date: 2025-01-02 DOI: 10.1146/annurev-pathmechdis-111523-023355
Hannah C Kinney
{"title":"Reflections on a Career in Pediatric Neuropathology, with a Note of Gratitude.","authors":"Hannah C Kinney","doi":"10.1146/annurev-pathmechdis-111523-023355","DOIUrl":"10.1146/annurev-pathmechdis-111523-023355","url":null,"abstract":"<p><p>I am honored to be asked by the journal to write this personal essay about my career in pediatric neuropathology-a life of immense satisfaction, meaning, and fulfillment. My motivation to enter this discipline is highlighted, as is my decision to perform brain research in the sudden infant death syndrome, the leading cause of postneonatal infant mortality in the United States today. I also touch upon collaborations, mentoring, and experiences along the way-especially with the light microscope. I close with thoughts about the future of the discipline from my perspective as a lifelong devotee.</p>","PeriodicalId":50753,"journal":{"name":"Annual Review of Pathology-Mechanisms of Disease","volume":" ","pages":"1-11"},"PeriodicalIF":28.4,"publicationDate":"2025-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141629248","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
Somatic Mosaicism in Brain Disorders. 脑部疾病中的体细胞嵌合。
IF 28.4 1区 医学
Annual Review of Pathology-Mechanisms of Disease Pub Date : 2025-01-01 Epub Date: 2025-01-02 DOI: 10.1146/annurev-pathmechdis-111523-023528
Rachel R Corrigan, Lauren M Mashburn-Warren, Hyojung Yoon, Tracy A Bedrosian
{"title":"Somatic Mosaicism in Brain Disorders.","authors":"Rachel R Corrigan, Lauren M Mashburn-Warren, Hyojung Yoon, Tracy A Bedrosian","doi":"10.1146/annurev-pathmechdis-111523-023528","DOIUrl":"10.1146/annurev-pathmechdis-111523-023528","url":null,"abstract":"<p><p>Research efforts over the past decade have defined the genetic landscape of somatic variation in the brain. Neurons accumulate somatic mutations from development through aging with potentially profound functional consequences. Recent studies have revealed the contribution of somatic mosaicism to various brain disorders including focal epilepsy, neuropsychiatric disease, and neurodegeneration. One notable finding is that the effect of somatic mosaicism on clinical outcomes can vary depending on contextual factors, such as the developmental origin of a variant or the number and type of cells affected. In this review, we highlight current knowledge regarding the role of somatic mosaicism in brain disorders and how biological context can mediate phenotypes. First, we identify the origins of brain somatic variation throughout the lifespan of an individual. Second, we explore recent discoveries that suggest somatic mosaicism contributes to various brain disorders. Finally, we discuss neuropathological associations of brain mosaicism in different biological contexts and potential clinical utility.</p>","PeriodicalId":50753,"journal":{"name":"Annual Review of Pathology-Mechanisms of Disease","volume":" ","pages":"13-32"},"PeriodicalIF":28.4,"publicationDate":"2025-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142127238","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
Immune Dysregulation in Obesity. 肥胖中的免疫失调。
IF 28.4 1区 医学
Annual Review of Pathology-Mechanisms of Disease Pub Date : 2025-01-01 DOI: 10.1146/annurev-pathmechdis-051222-015350
Zewen Jiang, Chihiro Tabuchi, Sarah G Gayer, Sagar P Bapat
{"title":"Immune Dysregulation in Obesity.","authors":"Zewen Jiang, Chihiro Tabuchi, Sarah G Gayer, Sagar P Bapat","doi":"10.1146/annurev-pathmechdis-051222-015350","DOIUrl":"10.1146/annurev-pathmechdis-051222-015350","url":null,"abstract":"<p><p>The immune system plays fundamental roles in maintaining physiological homeostasis. With the increasing prevalence of obesity-a state characterized by chronic inflammation and systemic dyshomeostasis-there is growing scientific and clinical interest in understanding how obesity reshapes immune function. In this review, we propose that obesity is not merely an altered metabolic state but also a fundamentally altered immunological state. We summarize key seminal and recent findings that elucidate how obesity influences immune function, spanning its classical role in microbial defense, its contribution to maladaptive inflammatory diseases such as asthma, and its impact on antitumor immunity. We also explore how obesity modulates immune function within tissue parenchyma, with a particular focus on the role of T cells in adipose tissue. Finally, we consider areas for future research, including investigation of the durable aspects of obesity on immunological function even after weight loss, such as those observed with glucagon-like peptide-1 (GLP-1) receptor agonist treatment. Altogether, this review emphasizes the critical role of systemic metabolism in shaping immune cell functions, with profound implications for tissue homeostasis across various physiological contexts.</p>","PeriodicalId":50753,"journal":{"name":"Annual Review of Pathology-Mechanisms of Disease","volume":"20 1","pages":"483-509"},"PeriodicalIF":28.4,"publicationDate":"2025-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143034733","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
Targeting Protein-Protein Interactions in Hematologic Malignancies. 靶向蛋白-蛋白相互作用在血液恶性肿瘤中的作用。
IF 28.4 1区 医学
Annual Review of Pathology-Mechanisms of Disease Pub Date : 2025-01-01 DOI: 10.1146/annurev-pathmechdis-031521-033231
Tomasz Cierpicki, Jolanta Grembecka
{"title":"Targeting Protein-Protein Interactions in Hematologic Malignancies.","authors":"Tomasz Cierpicki, Jolanta Grembecka","doi":"10.1146/annurev-pathmechdis-031521-033231","DOIUrl":"10.1146/annurev-pathmechdis-031521-033231","url":null,"abstract":"<p><p>Over the last two decades, there have been extensive efforts to develop small-molecule inhibitors of protein-protein interactions (PPIs) as novel therapeutics for cancer, including hematologic malignancies. Despite the numerous challenges associated with developing PPI inhibitors, a significant number of them have advanced to clinical studies in hematologic patients in recent years. The US Food and Drug Administration approval of the very first PPI inhibitor, venetoclax, demonstrated the real clinical value of blocking protein-protein interfaces. In this review, we discuss the most successful examples of PPI inhibitors that have reached clinical studies in patients with hematologic malignancies. We also describe the challenges of blocking PPIs with small molecules, clinical resistance to such compounds, and the lessons learned from the development of successful PPI inhibitors. Overall, this review highlights the remarkable success and substantial promise of blocking PPIs in hematologic malignancies.</p>","PeriodicalId":50753,"journal":{"name":"Annual Review of Pathology-Mechanisms of Disease","volume":"20 1","pages":"275-301"},"PeriodicalIF":28.4,"publicationDate":"2025-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143034745","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
Choroid Plexus Pathophysiology. 脉络丛病理生理学
IF 28.4 1区 医学
Annual Review of Pathology-Mechanisms of Disease Pub Date : 2025-01-01 Epub Date: 2025-01-02 DOI: 10.1146/annurev-pathmechdis-051222-114051
Ya'el Courtney, Alexandra Hochstetler, Maria K Lehtinen
{"title":"Choroid Plexus Pathophysiology.","authors":"Ya'el Courtney, Alexandra Hochstetler, Maria K Lehtinen","doi":"10.1146/annurev-pathmechdis-051222-114051","DOIUrl":"10.1146/annurev-pathmechdis-051222-114051","url":null,"abstract":"<p><p>This review examines the roles of the choroid plexus (ChP) in central nervous system (CNS) pathology, emphasizing its involvement in disease mechanisms and therapeutic potential. Structural changes in the human ChP have been reported across various diseases in case reports and descriptive work, but studies have yet to pin down the physiological relevance of these changes. We highlight primary pathologies of the ChP, as well as their significance in neurologic disorders, including stroke, hydrocephalus, infectious diseases, and neurodegeneration. Synthesizing recent research, this review positions the ChP as a critical player in CNS homeostasis and pathology, advocating for enhanced focus on its mechanisms to unlock new diagnostic and treatment strategies and ultimately improve patient outcomes in CNS diseases. Whether acting as a principal driver of disease, a gateway for pathogens into the CNS, or an orchestrator of neuroimmune processes, the ChP holds tremendous promise as a therapeutic target to attenuate a multitude of CNS conditions.</p>","PeriodicalId":50753,"journal":{"name":"Annual Review of Pathology-Mechanisms of Disease","volume":" ","pages":"193-220"},"PeriodicalIF":28.4,"publicationDate":"2025-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11884907/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142394983","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
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